Spinal Surgery, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, Guangdong, China.
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Life Sci. 2020 Jul 15;253:117730. doi: 10.1016/j.lfs.2020.117730. Epub 2020 Apr 26.
Stem cell therapy is widely employed in treating osteoarthritis (OA), and bone marrow-derived mesenchymal stem cells (BMSCs) has gradually become the most attractive new method for treating OA due to the benefit for cartilage tissue repair. However, the apoptosis in the neural stem cell transplantation severely decreases repairing efficacy. Icariin has been reported to exert multiple effects on BMSCs, including its proliferation, osteogenic, and chondrogenic differentiation. However, its effects on the injury induced by oxygen, glucose and serum deprivation (OGD) remains unknown. We prospectively investigated the role of ICA on rabbit BMSCs under conditions of OGD. Firstly, BMSCs were cultured under conditions of OGD, ICA relieved OGD-induced cell damage by promoting cell proliferation and suppressing apoptosis. Secondly, Markers of endoplasmic reticulum stress (ERs), ER stress IRE-1 pathway, and autophagy were both inhibited by ICA via inhibition of phosphor-extracellular regulated protein kinases (p-ERKs), p-P38, p-c-Jun N-terminal kinase (p-JNK) or si-MAPK. Finally, decrease of ERs marker levels enhanced protective effect of ICA against OGD-induced injury by limiting apoptosis and autophagy. Moreover, an autophagy inhibitor (3-methyladenine: 3-MA) contributed to a synergistic effect in conjunction with ICA, in promoting cell proliferation, suggesting that ICA exerts anti-ERs and anti-autophagy effects in OGD-treated BMSCs. Therefore, ICA protected rabbit BMSCs from OGD-induced apoptosis through inhibitory regulation of ERs-mediated autophagy related to the MAPK signaling pathway, which provided insights for a potential therapeutic strategy in OA.
干细胞治疗被广泛应用于治疗骨关节炎（OA），骨髓间充质干细胞（BMSCs）因有利于软骨组织修复而逐渐成为治疗 OA 的最具吸引力的新方法。然而，神经干细胞移植中的细胞凋亡严重降低了修复效果。淫羊藿苷已被报道对 BMSCs 具有多种作用，包括增殖、成骨和软骨分化。然而，其对氧、葡萄糖和血清剥夺（OGD）诱导的损伤的影响尚不清楚。我们前瞻性研究了 ICA 在 OGD 条件下对兔 BMSCs 的作用。首先，在 OGD 条件下培养 BMSCs，ICA 通过促进细胞增殖和抑制细胞凋亡来减轻 OGD 诱导的细胞损伤。其次，通过抑制磷酸化细胞外调节蛋白激酶（p-ERK）、p-P38、p-JNK 或 si-MAPK，ICA 抑制内质网应激（ERs）、ER 应激 IRE-1 途径和自噬标志物。最后，内质网应激标志物水平的降低通过限制细胞凋亡和自噬增强了 ICA 对 OGD 诱导损伤的保护作用。此外，自噬抑制剂（3-甲基腺嘌呤：3-MA）与 ICA 联合使用可产生协同作用，促进细胞增殖，表明 ICA 在 OGD 处理的 BMSCs 中发挥抗内质网应激和抗自噬作用。因此，ICA 通过抑制 MAPK 信号通路介导的内质网应激相关自噬来保护兔 BMSCs 免受 OGD 诱导的细胞凋亡，为 OA 的潜在治疗策略提供了思路。
